Suppose that
$N_1$ and
$N_2$ are closed smooth manifolds of dimension n that are homeomorphic. We prove that the spaces of smooth knots,
$ \operatorname {\mathrm {Emb}}(\mathrm {S}^1, N_1)$ and
$ \operatorname {\mathrm {Emb}}(\mathrm {S}^1, N_2),$ have the same homotopy
$(2n-7)$-type. In the four-dimensional case, this means that the spaces of smooth knots in homeomorphic
$4$-manifolds have sets
$\pi _0$ of components that are in bijection, and the corresponding path components have the same fundamental groups
$\pi _1$. The result about
$\pi _0$ is well-known and elementary, but the result about
$\pi _1$ appears to be new. The result gives a negative partial answer to a question of Oleg Viro. Our proof uses the Goodwillie–Weiss embedding tower. We give a new model for the quadratic stage of the Goodwillie–Weiss tower, and prove that the homotopy type of the quadratic approximation of the space of knots in N does not depend on the smooth structure on N. Our results also give a lower bound on
$\pi _2 \operatorname {\mathrm {Emb}}(\mathrm {S}^1, N)$. We use our model to show that for every choice of basepoint, each of the homotopy groups,
$\pi _1$ and
$\pi _2,$ of
$ \operatorname {\mathrm {Emb}}(\mathrm {S}^1, \mathrm {S}^1\times \mathrm {S}^3)$ contains an infinitely generated free abelian group.