Phase-dependent reorganization of circulating miRNA networks following short maximal exercise

Background Circulating microRNAs (miRNAs) are proposed biomarkers of exercise-induced stress and adaptation, yet acute responses are heterogeneous across studies. This suggests that miRNA regulation may depend on the temporal phase of the exercise response and on internal physiological stress, rather than on external workload alone. Objective To characterize phase-specific circulating miRNA responses to short maximal-effort exercise and examine their associations with internal physiological stress, recovery dynamics, and performance. Methods Eleven healthy young men performed a short maximal-effort cycling bout. Serum miR-103, miR-122, miR-144, and miR-486 were measured before exercise, immediately post-exercise, and 1 h post-exercise. Salivary cortisol and muscle tissue oxygen saturation (StO 2 ) were assessed as markers of endocrine and internal physiological stress. Responses were analyzed as log 2 -transformed fold changes across acute (after/before), recovery vs baseline (rest/before), and active recovery (rest/after) phases using non-parametric statistics and Spearman correlations. Results No uniform exercise-induced change in individual miRNAs was observed. Instead, responses were phase-specific: the acute phase showed coordinated behavior between miR-122 and miR-486 and alignment of molecular responses with exercise-induced tissue deoxygenation (ΔStO 2 ), whereas associations with performance were not evident. At 1 h post-exercise, miRNA levels largely returned toward baseline while salivary cortisol remained elevated. During active recovery, a strong coupling emerged between miR-103 and miR-144, consistent with coordinated metabolic-oxidative regulation. Conclusion Short maximal-effort exercise induces a phase-dependent reorganization of circulating miRNA coordination rather than a single uniform miRNA signature. Circulating miRNA dynamics appear to reflect internal physiological stress and early recovery processes more closely than external workload, supporting a phase-specific, network-based interpretation of miRNA regulation in exercise physiology.