Longitudinal Integrated Transcriptomic and Haematological Analysis of Male and Female Immunoregulatory Signatures in Short-Term Dry Immersion and Short-Term Spaceflight

Low Earth orbit spaceflight produces multi-system physiological changes arising from the space exposome, including microgravity, radiation, and other stressors. This thesis investigated longitudinal transcriptomic and haematological signatures of immune regulation during short-term dry immersion (STDI) and short-term spaceflight (STSF). Secondary analyses integrated transcriptomic and haematological data from ESA’s VIVALDI I (15 females) and VIVALDI II (19 males) five-day STDI studies and NASA’s SpaceX Inspiration4 (two females, two males) three-day spaceflight. Analyses principally examined NFκB- and Conserved Transcriptional Response to Adversity (CTRA)-associated genes, with broader immunoregulatory, hypoxia, and reactive oxygen species analyses. STDI produced modest differential gene expression but broader immune-haematological reorganisation. VIVALDI I demonstrated predominantly neutrophil-associated responses

during STDI that did not clearly resolve during Recovery Transition, while VIVALDI II demonstrated distinct STDI and Recovery Transition responses. Combined female-male analyses identified shared longitudinal and sex-dependent immunoregulatory patterns. Inspiration4 demonstrated no significant differentially expressed genes, but preliminary analyses identified immunoregulatory, haematological, hypoxia, and oxidative-stress associations. Collectively, findings demonstrate coordinated immune-haematological responses not captured by differential gene expression alone.