TORONTO -- After one of the most incredible performances in baseball history on Thursday, it was fair to wonder what two-way superstar Shohei Ohtani would do for an encore in Friday night’s series opener against the Blue Jays at Rogers Centre.

A day after he threw a one-hit shutout in Game 1 of a doubleheader and homered twice in Game 2 against the Tigers, Ohtani stayed hot by smacking his MLB-leading 39th homer in the first inning on the first pitch he saw from Kevin Gausman. But the same cramping issue in both legs that forced Ohtani to leave Thursday’s second game early caused him to exit on Friday.

He started to feel cramps after his third at-bat against the Blue Jays, and he was replaced by Michael Stefanic in a key situation in the ninth.

Stefanic pinch-hit for Ohtani with the bases loaded and one out, but he struck out looking on a borderline call on an outside 3-2 pitch from closer Jordan Romano. It was yet another issue with runners in scoring position for the Angels, as they went 0-for-7 in those situations in a 4-1 loss in the opener.

Manager Phil Nevin said Ohtani's cramping issue is in both legs, but he should be fine.

“We’ll evaluate him [on Saturday] when he gets up, but he’s dealing with cramping right now,” Nevin said. “He’s put in a lot of work the last few days.”

It was a frustrating defeat for the Angels, who are trying to chase the Blue Jays in the AL Wild Card standings. The loss dropped the Angels (54-50) to four games behind Toronto (58-46) for the third and final Wild Card spot. The Halos are 1-3 against the Blue Jays this year, which puts them in danger of losing an important tiebreaker, now that there are no Game 163s.

Ohtani, who also saw his next start on the mound pushed back to Thursday against the Mariners due to his heavy workload in Detroit, crushed a first-pitch fastball from Gausman for his fourth homer over his past five games. With 39 blasts through 104 team games, Ohtani is on pace to hit 61 homers this season.

But it was the only run the Angels could muster despite having their chances, especially in the seventh and ninth innings. They loaded the bases with nobody out in the seventh, but couldn’t score, as reliever Erik Swanson shut them down after Gausman exited. The Halos also had the bases loaded with one out in the ninth, and they couldn’t get any runs across.

“We certainly had our chances,” Nevin said. “Having the bases loaded and not getting one across hurts. And in the ninth, Stefanic had a great at-bat. I thought he walked, and it could’ve been different after that. But we just have to have better at-bats with the bases loaded and nobody out.”

The lack of offense spoiled a mostly solid outing from right-hander Lucas Giolito, who made his Angels debut after being acquired along with reliever Reynaldo López in a trade with the White Sox on Wednesday. Giolito went 5 1/3 innings, allowing three runs on six hits and a walk with five strikeouts.

He was handed an early lead with Ohtani’s homer, but he gave up a solo shot to Matt Chapman in the second to tie the game before surrendering a solo blast to Danny Jansen in the third that gave the Blue Jays the lead. Chapman’s homer came on a 3-2 fastball that caught too much of the plate, while Jansen’s came on a 1-0 fastball over the middle.

“Not the best,” Giolito said of his outing. “I felt relatively sharp, throwing a lot of strikes. But they hammered my mistakes pretty good. A couple of home runs and I was in a tough situation there in the sixth inning. I'd like to be a little bit sharper than that.”

Giolito gave up another run in the sixth on an RBI double from Bo Bichette. After intentionally walking Vladimir Guerrero Jr. with one out, it appeared the right-hander was going to get out of the inning without further damage. But shortstop Andrew Velazquez made an error on a potential inning-ending double play, and that was it from Giolito after 73 pitches.

Reliever José Soriano struck out Chapman and Daulton Varsho to escape further trouble.

“If we turn a double play for him, he’s going back out there to pitch the seventh,” Nevin said. “But with the way Soriano has been throwing it, we needed a strikeout and he got two. But I thought Lucas threw the ball really well.”