In this thesis, we assessed the impact of depth on microbiota and bioactivity of sponges from shallow water to mesophotic zone and beyond (until approximately 1500 m). Understanding both the prokaryotic community and metabolite profiles of sponges in relation to depth will provide important insights for marine ecology and future bioprospecting efforts of bioactive compounds from marine sponges and their associated microbes. We observed that depth significantly affected prokaryotic community composition and at the same time also influenced metabolite profiles and antimicrobial activities in shallow as well as deep-sea sponges. In contrast, depth did not consistently affect cultivability of sponge-associated bacteria as opposed to the source of inocula and the growth media. Future research should be focused on metagenomics in combination with innovative cultivation strategies in order to obtain a clearer insight on prokaryotic community composition and diversity of secondary metabolite biosynthesis gene clusters of sponges across depth gradients.