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DETROIT — Clay Holmes picked the wrong time to miss the strike zone with a few pitches.

Already, the Mets right-hander had walked Colt Keith in Wednesday’s fifth inning.

But Holmes retired Gleyber Torres for the second out and was in position to escape the inning with the score 1-1, then perhaps pitch into the sixth.

A second walk in the inning, to Kerry Carpenter, changed the script. Holmes was removed, and Gregory Soto unloaded a wild pitch before allowing a single to Riley Greene for two runs in the 6-2 loss to the Tigers at Comerica Park.

“I came out today and my stuff was really good — probably some of the best stuff I have had early on and kind of really throughout,” Holmes said. “I feel like overall I am in a good place. It’s just competing. And this is the time of year where you really have to execute and each pitch matters.”

Holmes was asked if he was surprised manager Carlos Mendoza removed him after he walked Carpenter.

“I try not to play that game on the mound,” Holmes said. “It’s probably not the best place to be when you try to think through that. Ultimately, I was just trying to win the inning there.”

Francisco Alvarez played a second straight game behind the plate in a rehab appearance for Triple-A Syracuse. He hit a grand slam and drew a walk in four at-bats

The catcher is eligible for removal from the injured list, but Mendoza wasn’t ready to say after Wednesday’s game if Alvarez will be activated on Friday. Alvarez is rehabbing a ligament sprain in his right thumb and broken pinkie on his left hand.

Nolan McLean is the second major league pitcher, according to Opta Sports, to go 4-0 with a sub-1.50 ERA and at least 25 strikeouts in his first four starts. The other was Fernando Valenzuela with the Dodgers in 1981. McLean’s 28 strikeouts through his first four starts are the most in franchise history. Tylor Megill, Dwight Gooden, Matt Harvey and Dick Selma previously shared the record at 26.

McLean is the only Mets pitcher with four wins in as many starts to begin his major league career.