CHICAGO — The Twins dropped the rubber match of a three-game set to the Cubs, 8-2, on Wednesday afternoon.

That was the least of their worries.

Starter Joe Ryan, the right-hander who has been the Twins’ No. 2 starter all season, left the game after calling for the trainer four pitches into his third inning of work at Wrigley Field.

The Cubs were up 2-1 and Ryan had faced one over the minimum with a pair of strikeouts, but after throwing an 83.3 mph splitter to Pete Crow-Armstrong for a ball, he stepped off the mound and signaled to the dugout.

Michael Busch and Ian Happ homered for the Cubs, and Selya Suzuki and Isaac Paredes drove in runs with a bases-loaded walk and sacrifice fly, respectively, as Chicago won for the fifth time in seven games.

The Twins, who have a big four-game series this weekend against Cleveland at Target Field, were planning to call Louie Varland up from Class AAA St. Paul to make one of the starts in Friday’s double-header — Bailey Ober will throw the other — but now Minnesota might need a longer-term rotation replacement.

The immediate diagnosis for Ryan was tightness in the triceps, which commonly presents as elbow pain.

Pending the Guardians’ game against Arizona on Wednesday evening, the second-place Twins were four games behind Cleveland in the American League Central, and 0-5 against the Guardians this season.

The Twins took a 1-0 lead in the first when Matt Wallner drove in Trevor Larnach (walk) with a two-out double off starter Javier Assad. Busch tied it with a home run off Ryan in the Cubs’ half of the inning before Brooks Lee brought home Carlos Santana (single) with a grounder in the second inning.

Then Ryan was done and it all kind of unraveled.

Trevor Richards (0-1) replaced Ryan on short notice and struggled. He walked five and gave up three runs in two-third of an inning, one on a wild pitch, one on a walk to Selya Suzuki and one on a sac fly by Paredes.

That erased the Twins’ 2-1 lead, and Happ added a two-run home run off Cole Sands in the fourth inning. The Cubs stole three bases, all resulting runs — one in the third inning, two in the eighth.

The Twins burned through four relievers — Richards, Sands, Josh Winder and Caleb Thielbar — but have an off day Thursday.

It would be a completely forgettable game if it weren’t for Ryan’s anomalous start. Among Twins starters this season, only Ober has been more consistently good than Ryan, who entered the game with a 7-7 record and 3.59 earned-run average and 13 quality starts.

Before Wednesday’s game, manager Rocco Baldelli said Ryan, 28, “has actually improved in almost every area. Everything’s kind of ticked up.”

“So, I think you see more of a compounded effect than just a simple like, ‘Oh, he’s slightly better. He’s just slightly better.’ No, he’s better everywhere you look.”

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