The 21-cm signal provides a novel avenue to measure the thermal state of the Universe during cosmic dawn and reionization (redshifts z∼5–30), and thus to probe energy injection from decaying or annihilating dark matter (DM). These DM processes are inherently inhomogeneous: both decay and annihilation are density-dependent, and furthermore, the fraction of injected energy that is deposited at each point depends on the gas ionization and density, leading to further anisotropies in absorption and propagation. In this work, we develop a new framework for modeling the impact of spatially inhomogeneous energy injection and deposition during cosmic dawn, accounting for ionization and baryon density dependence, as well as the attenuation of propagating photons. We showcase how this first completely inhomogeneous treatment affects the predicted 21-cm power spectrum in the presence of exotic sources of energy injection, and forecast the constraints that upcoming HERA measurements of the 21-cm power spectrum will set on DM decays to photons and to electron/positron pairs. These projected constraints considerably surpass those derived from CMB and Lyman-α measurements, and for decays to electron/positron pairs they exceed all existing constraints in the sub-GeV mass range, reaching lifetimes of ∼1028 s. Our analysis demonstrates the unprecedented sensitivity of 21-cm cosmology to exotic sources of energy injection during the cosmic dark ages. Our code, 21cm, includes all these effects and is publicly available in an accompanying release. Published by the American Physical Society 2025
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