Andreev-Andrievskiy, A. A.; Mashkin, M. A.; Drugova, S. V.; Shurshakov, V. A.; Popov, D. V.; Tarasova, O. S.; Buravkova, L. B.; Vinogradova, O. L.; Sychev, V. N.; Orlov, O. I.; Bion-M 2 Team,

The combined effects of microgravity and deep-space radiation on whole-body physiology remain poorly quantified for future crewed missions. Bion-M 2, a 30-day high-latitude biosatellite carrying group-housed mice, achieved an ISS-comparable total dose with an enriched galactic cosmic ray fraction, approximating conditions beyond low-Earth orbit. A quantitative atlas of 73 physiological endpoints revealed pronounced antigravity muscle atrophy, immune and gastrointestinal remodeling, and delayed recovery of hematologic and visceral indices through 30 days post-landing. A dry-food-hydrogel diet transformed this response into a stress-dominated, densely interconnected physiological state. Pharmacological Nrf2 activation with omaveloxolone preserved hindlimb muscle mass at ground-control levels and protected visceral organs. These findings establish a systems-level baseline for mammalian adaptation to a deep-space-analog orbit and identify diet and Nrf2 activation as tractable countermeasure levers.