Background: Both pathological conditions and hibernation can affect the barrier function of small intestine mucosa. However, the effect of hibernation on the barrier function of colonic mucosa remains unclear. Methods: We investigated morphological changes in colonic mucosa, the concentrations of specific proteins and molecules, and the enzymatic activity of diamine oxidase (DAO), in serum and colonic tissue; the expression of tight junction proteins and mucin, and the changes in inflammatory, farnesoid X receptor (FXR)–small heterodimer partner (SHP), and apoptosis-related molecules that could play a role in gut permeability changes in Daurian ground squirrels in summer active (SA), late torpor (LT), and interbout arousal (IBA) periods. Results: The results show that hibernation reduced the thickness of the colonic mucosa and the depth of the crypt, decreased the number of goblet cells (GCs), and damaged the structure of some microvilli. The concentrations of proteins and molecules, and the enzymatic activity of DAO, were all increased in the serum and colon, and the localization of tight junction proteins and mucin in the colonic mucosa were altered (compensatory response). Although the ground squirrels ate during the interbout arousal period, the changes remained similar to the response to torpor. Inflammation, apoptosis–anti-apoptosis, and FXR–SHP signaling may be involved in the possible changes in intestinal gut permeability during the torpor–arousal cycle in Daurian ground squirrels. In addition, periodic interbout arousal may play an inflammation-correcting role during the long hibernation season of Daurian ground squirrels.

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41Whether differences in regulation of protein metabolism and regeneration are involved in the 42 different phenotypic adaptation mechanisms of muscle hypertrophy and atrophy in hibernators? 43Two fast-type muscles (diaphragm and gastrocnemius) in summer active and hibernating Daurian 44 ground squirrels were selected to detect changes in cross-sectional area (CSA), fiber type 45 distribution, and protein expression indicative of protein synthesis metabolism (protein expression 46 of P-Akt, P-mTORC1, P-S6K1, and P-4E-BP1), protein degradation metabolism (MuRF1, atrogin-47 1, calpain-1, calpain-2, calpastatin, desmin, troponin T, Beclin1, and LC3-II), and muscle 48 regeneration (MyoD, myogenin, and myostatin). Results showed the CSA of the diaphragm muscle 49 increased significantly by 26.1%, whereas the CSA of the gastrocnemius muscle decreased 50 significantly by 20.4% in the hibernation group compared with the summer active group. Both 51 muscles displayed a significant fast-to-slow fiber-type transition in hibernation. Our study further 52 indicated that increased protein synthesis, decreased protein degradation, and increased muscle 53 regeneration potential contributed to diaphragm muscle hypertrophy, whereas decreased protein 54 synthesis, increased protein degradation, and decreased muscle regeneration potential contributed 55 to gastrocnemius muscle atrophy. In conclusion, the differences in muscle regeneration and 56 regulatory pattern of protein metabolism may contribute to the different adaptive changes observed 57 in the diaphragm and gastrocnemius muscles of ground squirrels. 58 59