Transcriptomic Profiling Reveals Early Molecular Adaptations to Resistance Exercise During Disuse Muscle Atrophy with Complementary Automated H&E-Based Muscle Morphometry

Although resistance exercise effectively attenuates disuse muscle atrophy, studies examining both quantitative muscle morphometry and transcriptomic responses during early adaptation remain limited. To comprehensively evaluate these adaptations, we performed automated Hematoxylin and Eosin stain (H&E)-based quantitative morphometry alongside transcriptomic profiling in a mouse model of hindlimb immobilization with or without resistance exercise. Resistance exercise partially restored muscle fiber atrophy and restored muscle morphology. Transcriptomic profiling identified 76 differentially expressed genes and revealed coordinated alterations involving metabolic regulation, immune/inflammatory responses, and extracellular matrix remodeling, rather than a single dominant signaling pathway. Functional enrichment analysis further highlighted cytokine-mediated signaling, extracellular matrix organization, and metabolic pathways associated with the early response to resistance exercise. Together, these findings demonstrate that automated H&E-based morphometry, alongside transcriptomic profiling, provides complementary structural and molecular insights into the early adaptive response to resistance exercise and offers a practical framework for future studies of skeletal muscle remodeling.