Sponges are sessile, evolutionarily ancient and filter-feeding invertebrates that are functionally important members of the benthic environment. Sponges, being complex holobiont systems, constantly host a diverse variety of microbiota that contribute to the growth, chemical defence and immune system of sponges. Sponge holobionts are indicators of environmental stress because they actively respond to perturbations by maintaining homeostasis or disturbing the sponge–microbiota dynamic equilibrium, leading to an imbalance of dysbiotic and disease conditions, causing mass mortality of sponges. In this chapter, we will discuss the sponge disease and variation in sponge microbiome and gene or protein expression in response to environmental changes such as ocean warming, acidification and pollution. Consequently, some sponge biosensors and indicators of environmental and climatic change are suggested. Future research should utilize metagenomic, single-cell genomics and transcriptomic approaches to understand sponge holobiont’s response to environmental stress and climatic changes at molecular and cellular levels, as well as analysis of complex molecular mechanisms of interaction between sponge host and its symbiotic microbes in a true holobiont approach.