The findings from this study provides a comprehensive descriptions of skeletal muscle transcriptome that suggest a middle-distance running exercise resulted in the most significantly altered differentially expressed genes (DEG). The pathways where these DEG are primarily involved are important for regulating stress responses. Therefore, mice assigned to the HFD-50% may have been better able to handle the impact of diet-induced stress and may be more efficient at compensating the detrimental effects of HFD consumption.