Marine sponges and their microbial symbiotic communities are rich sources of diverse natural products (NPs) that often display biological activity, yet little is known about their global distribution landscape and the symbionts that produce them. As the majority of sponge symbionts remain uncultured, it is a challenge to characterize their NP biosynthetic pathways, assess their prevalence within the holobiont and measure their diversity across sponge taxa and environments. Here, we explore the

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... icrobial biosynthetic landscapes of three sponge species from the Atlantic Ocean and the Mediterranean Sea. This dataset reveals striking novelty in its encoded biosynthetic potential, with less than 1% of the recovered gene cluster families (GCF) showing similarity to any characterized biosynthetic gene cluster (BGC). When zooming in on the microbial communities of each sponge, we observed higher variability of both secondary metabolic and taxonomic profiles between sponge species than within species. Nonetheless, we also identified conservation of GCFs, with 20% of sponge GCFs being shared between at least two sponge species, and a true GCF core comprised of 6% of GCFs shared across all species. Within this functional core, we identified a set of widespread and diverse GCFs encoding nonribosomal peptide synthetases (NRPS) that are potentially involved in the production of diversified ether lipids, as well as GCFs putatively encoding the production of highly modified proteusins. The present work contributes to the small, yet growing body of data characterizing NP landscapes of marine sponge symbionts, and to the cryptic biosynthetic potential contained in this environmental niche.