Eight years after he was the Republican presidential nominee, Sen. John McCain appears headed toward his toughest re-election fight yet, in no small part because of presumptive GOP presidential standard-bearer Donald Trump.

Rep. Ann Kirkpatrick, the Democratic Senate candidate who is neck-and-neck with McCain in polls, has relentlessly gone after McCain for the senator’s support – no matter how tepid – of Trump.

McCain has hardly shown enthusiasm for Trump, only saying he would support the party’s nominee (while planning to skip the GOP convention in Cleveland). And he’s privately warned that Trump could hurt his own bid. Politico reported on audio from a fundraiser where McCain is heard saying, “If Donald Trump is at the top of the ticket, here in Arizona, with over 30 percent of the vote being the Hispanic vote, no doubt that this may be the race of my life.”

But Kirkpatrick’s campaign is hammering any connection it can between McCain and Trump, settling for nothing short of denunciation by the sitting senator.

“John McCain’s supporting Donald Trump despite declaring Trump ‘dangerous’ and characterizing Trump's supporters as ‘crazies,’” Kirkpatrick campaign spokesman D.B. Mitchell told FoxNews.com. “It's clear McCain's 'straight talk' days are over.”

McCain’s campaign, meanwhile, has blasted Kirkpatrick as “siding with the liberal establishment.”

The race is a snapshot of the conflicted relationship high-profile Republican candidates across the country could have with the presumptive presidential nominee. The jury is out on whether, on balance, he would help or hurt congressional candidates. 

But for McCain, Trump’s impact is even being felt in the Republican primary.  

One of his opponents, Alex Meluskey, a businessman and talk radio host, cited an internal campaign poll showing most respondents would be more likely to vote for a businessman who never ran for office over a career politician – and claimed the “Trump phenomenon” would be good for him.

“Any time you have an outsider businessman, that absolutely favors us,” Meluskey told FoxNews.com.

McCain also is facing opposition from Kelli Ward, a doctor who resigned her state Senate seat last year to run full time for the U.S. Senate. She is touting a resounding GOP straw poll victory over McCain earlier this month at the Arizona Republican State Convention and is pushing a campaign theme of “bold, fresh and fearless,” to contrast McCain’s status as a longtime Washington insider.

The Republican primary is Aug. 30, just one day after McCain turns 80.

But it’s the expected November race that’s causing headaches for the senator this year. During his five decisive Senate victories, the relatively moderate McCain has rarely had a real challenge in the general election.

“He usually has more concern in the state over who his primary challenger will be," Barbara Norrander, a political science professor at the University of Arizona, told FoxNews.com. “Democrats have had a hard time recruiting someone viable to oppose him.”

This year could be different. A Merrill Poll in March found McCain leading Kirkpatrick by just one point, while a Behavior Research Center poll in April showed the two tied at 42-42 percent.

Kirkpatrick, a former Arizona state legislator, was first elected to the House in 2008. She was voted out of office during the Republican wave of 2010, then ran again and won in 2012 – and withstood another Republican wave in 2014 to keep her seat.

McCain has more than $5.5 million cash on hand, according to the Federal Election Commission. That overwhelms every other opponent, as Kirkpatrick has $1.3 million, Ward has $210,792 and Meluskey has $163,764, according to FEC reports as of March 31.

The McCain campaign is going after Kirkpatrick for her support of ObamaCare, and says Arizonans are facing a 21 percent increase in health insurance deductibles, while 59,000 Arizonans lost their insurance when the state’s co-op was removed from the federal marketplace.

“Even as independent analysts predict a dramatic rise in health care costs and more insurers contemplate exiting a crumbling marketplace, Congresswoman Kirkpatrick offers no solutions for the people of Arizona,” McCain campaign spokeswoman Lorna Romero said in a statement. “Instead, she is siding with the liberal establishment and ducking questions about President Obama’s failed health care law.”

On the issue McCain fears could be troublesome because of Trump, he and Kirkpatrick both agree on a pathway to citizenship for some 11 million illegal immigrants in the United States, but clash on the so-called Dream Act. Further, Kirkpatrick doesn’t necessarily have an automatic advantage with Hispanic voters.

The U.S. Hispanic Chamber of Commerce endorsed McCain in April. Last year, the liberal group Emily’s List, backing Kirkpatrick, criticized another Latino coalition endorsing McCain as a “taco shop,” and said McCain put on a “sombrero to pander.” The Arizona Republic editorial board denounced the Emily’s List stereotypes.