Mechanical unloading via acoustic force counterbalancing shares transcriptomic and functional features with spaceflight responses in Caenorhabditis elegans

The loss of gravitational load during spaceflight produces conserved physiological and transcriptomic adaptations, but orbital experiments remain scarce, and the ground-based simulators in common use, including clinostats, rotating-wall vessels, and random positioning machines, reorient the gravity vector rather than canceling the gravitational force itself.The mechanically unloaded state is therefore only partially reproduced.Here we applied a waveguided hydro-ultrasonic microgravity device (WHMD), an acoustic force-counterbalancing platform previously reported in our group, to Caenorhabditis elegans, and obtained the first transcriptome-wide characterization of the response to mechanical unloading on this platform.WHMD exposure produced a coordinated transcriptional response, with suppression of stimulus-detection, sensory, and feeding programs and induction of biological-oxidation, detoxification, cell-cycle, and germline gene sets.When International Space Station datasets were reanalyzed within the same enrichment framework, 77-81% of biological-process terms, 84% of molecular-function terms, and 63% of cellular-component terms agreed in enrichment direction with WHMD, revealing substantial pathway-level concordance between WHMD and spaceflight responses.Functionally, WHMD-exposed worms showed reduced bending amplitude (mean -12%, maximum -26%) with increased bending frequency (+20%) and no developmental delay, consistent with the neuromuscular changes reported in flown worms.Acoustic force counterbalancing thus provides a mechanistically distinct and practical platform for the study of gravity-dependent biology.