Dynamic Transcriptomic Network Responses to Divergent Acute Exercise Challenges in Young Adults

Acute exercise elicits dynamic transcriptional changes that, when repeated, form the fundamental basis of adaptations in health, resilience, and performance. While moderate-intensity endurance training combined with conventional resistance training (traditional, TRAD) is often prescribed and recommended by public health guidance, high-intensity training combining maximal-effort intervals with intensive, limited-rest resistance training is a time-efficient alternative that may be used tactically (HITT) to seek whole body health benefits. Mechanisms of action of these distinct doses are incompletely characterized and have not been directly compared. We assessed transcriptome-wide responses in skeletal muscle and circulating extracellular vesicles (EVs) to a single exercise bout in young adults randomized to TRAD (n=21, 12M/9F, 22±3y) or HITT (n=19, 11M/8F, 22±2y). Next-generation sequencing captured small, long, and circular RNA in muscle and EVs. Analysis identified differentially expressed transcripts (|log2FC|>1, FDR≤0.05) immediately (h0, EVs only), h3, and h24 post-exercise within and between exercise doses. Additionally, all apparently responsive transcripts (FDR