Mesophotic reefs, located in the "Twilight Zone" of the ocean, are coral reefs that exist in relatively deep waters ranging from approximately 30 to 150 m below the surface. These reefs are situated just beyond the reach of conventional SCUBA diving and are typically explored using advanced diving techniques or with the aid of submersibles. In the present study, we used a state-of-the-art submersible to sample 26 sponge specimens belonging to 11 species. High (HMA) or low (LMA) microbial abundance status was assigned to species based on TEM imagery. Prokaryotic communities associated with these sponges were, furthermore, assessed using high-throughput sequencing. Proteobacteria, Chloroflexi, Actinobacteriota, and Acidobacteriota were the most abundant phyla overall. HMA/LMA status proved to be a highly significant predictor of prokaryotic composition. HMA sponges also tended to be more diverse in terms of richness and evenness than LMA sponges. 14 predictor-classes were identified using an exploratory technique based on machine learning including classes within the phyla Chloroflexi (e.g., Dehalococcoidia and JG30-KF-CM66) and Acidobacteriota (Thermoanaerobaculia and Subgroups 11 and 21). Previous studies have demonstrated the prevalence of the HMA/LMA dichotomy in shallow waters and, recently, the deep sea. Our results demonstrate its prevalence in the mesophotic realm.