Abstract
Prolonged spaceflight is associated with skeletal muscle atrophy, but the molecular mechanisms linking immune dysregulation, circadian disruption, and metabolic remodeling remain poorly understood. This study performed RNA-seq transcriptomic profiling of tibialis anterior muscle from mice flown on the International Space Station for 38 days, using data from NASA's Rodent Research-23 mission (OSD-576). Comparing flight mice with habitat ground controls, 311 genes were differentially expressed (FDR 1.5). Flight mice showed an elevated expression of acute phase and stress response genes, including Lcn2 (log2FC = +3.65), Orm1 (+3.87), Pnmt (+3.07), and Cdkn1a (+2.39), and reduced expression of metabolic, circadian, and chemokine genes, including Nmrk2 (−3.90), Dbp (−1.96), Cxcl10 (−2.34), Ccl2 (−2.68), S100a8 (−2.61), and S100a9 (−2.97). Overrepresentation analysis identified shared gene membership (not directional concordance) with published gene sets for idiopathic pulmonary fibrosis, acute myocardial infarction, dilated cardiomyopathy, and colitis. Several overlapping genes moved in opposite directions relative to the disease reference sets. The findings are consistent with immunometabolic transcriptional remodeling of skeletal muscle, characterized by acute phase activation along with suppression of chemokine signaling, circadian control, and energy metabolism.